This proposal has the major objective of determining the contribution of macrophages to immunodepression of aging. Using a Fischer 344 rat model consisting of aged animals housed under germ-free, gnotobiotic and conventional conditions, in vitro assays of T lymphocyte function are being monitored to determine if increased activity of "suppressor macrophages" with age is an inherent physiological process or whether continuous external stimuli from environmental microflora result in expansion and activation of the suppressor population. Density gradient centrifugation is being used to identify macrophage subpopulation which function as suppressor cells. Analysis of culture supernates for prostaglandins is being performed to determine their role as mediators of immunodepression in aging.